There is a need for an in vitro substrate for the cultivation of hepatitis viruses. Hepatocytes would seem a logical choice, but it is very difficult to obtain and maintain primate hepatocytes in culture. We are attempting to develop hepatocyte-hepatoma hybridomas of primate origin. Such hybrid cells would be expected to have the receptor sites and metabolic systems suitable for synthesis of hepatitis viruses and the ability of hepatoma cells to multiply indefinitely in vitro. Methods for the selection of hybrid cells without drug markers (i.e. use of vital dyes) have been developed. These and other vital dyes are being studied for their ability to detect metabolic changes in cells that are infected with viruses.